Ocular Versus Oral Propranolol for Prevention and/or Treatment of Oxygen-Induced Retinopathy in a Rat Model

Qadri, Areej; Cai, Charles L.; Deslouches, Karen; Siddiqui, Faisal; Aranda, Jacob V.; Beharry, Kay D.

doi:10.1089/jop.2020.0092

Cited by 5 publications

(3 citation statements)

References 56 publications

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“…The same holds true for oral administration of propranolol, another phase 1 approach. Although it has been shown to prevent astrocyte degeneration resulting from hypoxic injuries, it failed to completely prevent ROP and is ineffective against inflammation ( 61 ). Another phase 1 treatment approach is intravenous injections of recombinant human IGF1 complexed with its binding protein (rhIGF1/rhIGFBP3).…”

Section: Discussionmentioning

confidence: 99%

A single intravenous injection of cyclosporin A–loaded lipid nanocapsules prevents retinopathy of prematurity

et al. 2022

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Retinopathy of prematurity (ROP) is a retinal disease that threatens the vision of prematurely born infants. Severe visual impairment up to complete blindness is caused by neovascularization and inflammation, progressively destroying the immature retina. ROP primarily affects newborns in middle- and low-income countries with limited access to current standard treatments such as intraocular drug injections and laser- or cryotherapy. To overcome these limitations, we developed a nanotherapeutic that effectively prevents ROP development with one simple intravenous injection. Its lipid nanocapsules transport the antiangiogenic and anti-inflammatory cyclosporin A efficiently into disease-driving retinal pigment epithelium cells. In a mouse model of ROP, a single intravenous injection of the nanotherapeutic prevented ROP and led to normal retinal development by counteracting neovascularization and inflammation. This nanotherapeutic approach has the potential to bring about a change of paradigm in ROP therapy and prevent millions of preterm born infants from developing ROP.

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Section: Discussionmentioning

confidence: 99%

A single intravenous injection of cyclosporin A–loaded lipid nanocapsules prevents retinopathy of prematurity

et al. 2022

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“…A similar effect was described some years later by Cammalleri et al administering propranolol to OIR mice ( 96 ). More recently, Qadri et al, demonstrated that propranolol prevented retinal astrocyte degeneration evoking an indirect neuroprotective effect if one considers the relevant role played by astrocytes in retinal function ( 97 ).…”

Section: Propranolol In Mice With Oxygen Induced Retinopathymentioning

confidence: 99%

Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression

Pascarella,

Scaramuzzo,

Pini

et al. 2024

Front. Pediatr.

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Despite the evident progress in neonatal medicine, retinopathy of prematurity (ROP) remains a serious threat to the vision of premature infants, due to a still partial understanding of the mechanisms underlying the development of this disease and the lack of drugs capable of arresting its progression. Although ROP is a multifactorial disease, retinal vascularization is strictly dependent on oxygen concentration. The exposition of the retina of a preterm newborn, still incompletely vascularized, to an atmosphere relatively hyperoxic, as the extrauterine environment, induces the downregulation of proangiogenic factors and therefore the interruption of vascularization (first ischemic phase of ROP). However, over the following weeks, the growing metabolic requirement of this ischemic retina produces a progressive hypoxia that specularly promotes the surge of proangiogenic factors, finally leading to proliferative retinopathy (second proliferative phase of ROP). The demonstration that the noradrenergic system is actively involved in the coupling between hypoxia and the induction of vasculogenesis paved the way for a pharmacologic intervention aimed at counteracting the interaction of noradrenaline with specific receptors and consequently the progression of ROP. A similar trend has been observed in infantile hemangiomas, the most common vascular lesion of childhood induced by pre-existing hypoxia, which shares similar characteristics with ROP. The fact that propranolol, an unselective antagonist of β1/2 adrenoceptors, counteracts the growth of infantile hemangiomas, suggested the idea of testing the efficacy of propranolol in infants with ROP. From preclinical studies, ongoing clinical trials demonstrated that topical administration of propranolol likely represents the optimal approach to reconcile its efficacy and maximum safety. Given the strict relationship between vessels and neurons, recovering retinal vascularization with propranolol may add further efficacy to prevent retinal dysfunction. In conclusion, the strategy of contrasting precociously the progression of the disease appears to be more advantageous than the current wait-and-see therapeutic approach, which instead is mainly focused on avoiding retinal detachment.

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“…In this respect propranolol, in the mouse OIR model, was found to counteract visual dysfunction by protecting retinal cells through the direct modulation of survival mechanisms such as the stimulation of autophagy and the inhibition of apoptosis (Cammalleri et al, 2017). A recent study demonstrated that, in a rat model of OIR, topical propranolol not only reduced retinal vascular damage but also prevented astrocytes degeneration (Qadri et al, 2021), suggesting that propranolol may play an indirect neuroprotective effect if one considers the relevant role played by astrocytes in retinal function. The neuroprotective properties of propranolol together with its anti-angiogenic activity during the hypoxic stages indicate an actual efficacy of the drug.…”

Section: Treatment With Propranololmentioning

confidence: 99%

Decoupling Oxygen Tension From Retinal Vascularization as a New Perspective for Management of Retinopathy of Prematurity. New Opportunities From β-adrenoceptors

et al. 2022

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Retinopathy of prematurity (ROP) is an evolutive and potentially blinding eye disease that affects preterm newborns. Unfortunately, until now no conservative therapy of active ROP with proven efficacy is available. Although ROP is a multifactorial disease, premature exposition to oxygen concentrations higher than those intrauterine, represents the initial pathogenetic trigger. The increase of oxygenation in a retina still incompletely vascularized promotes the downregulation of proangiogenic factors and finally the interruption of vascularization (ischemic phase). However, the increasing metabolic requirement of the ischemic retina induces, over the following weeks, a progressive hypoxia that specularly increases the levels of proangiogenic factors finally leading to proliferative retinopathy (proliferative phase). Considering non-modifiable the coupling between oxygen levels and vascularization, so far, neonatologists and ophthalmologists have “played defense”, meticulously searching the minimum necessary concentration of oxygen for individual newborns, refining their diagnostic ability, adopting a careful monitoring policy, ready to decisively intervene only in a very advanced stage of disease progression. However, recent advances have demonstrated the possibility to pharmacologically modulate the relationship between oxygen and vascularization, opening thus the perspective for new therapeutic or preventive opportunities. The perspective of a shift from a defensive towards an attack strategy is now at hand.

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Ocular Versus Oral Propranolol for Prevention and/or Treatment of Oxygen-Induced Retinopathy in a Rat Model

Cited by 5 publications

References 56 publications

A single intravenous injection of cyclosporin A–loaded lipid nanocapsules prevents retinopathy of prematurity

A single intravenous injection of cyclosporin A–loaded lipid nanocapsules prevents retinopathy of prematurity

Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression

Decoupling Oxygen Tension From Retinal Vascularization as a New Perspective for Management of Retinopathy of Prematurity. New Opportunities From β-adrenoceptors

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